Since time immemorial, herpes viral infections have been a scourge of mankind and many important domestic animals. The herpes family of virus includes herpes simplex virus (types 1 and 2) responsible for cold sores and genital lesions, respectively; varicella zoster virus which causes chicken pox and shingles; and the Epstein-Barr virus which causes infectious mononucleosis. Although some significant advances have been made in the last decade in antiviral therapy, the need for effective, safe therapeutic agents for treating herpes viral infections continues to exist. For a recent review of current therapeutic agents in this area, see M. C. Nahata, "Antiviral Drugs: Pharmacokinetics, Adverse Effects and Therapeutic Use", J. Pharm. Technol., 3, 100 (1987).
It has now been found that a group of naphthoquinone derivatives, having a wide margin of safety, are useful for combatting herpes viral infections. The naphthoquinone derivatives are known having been cribed previously as antipsoriatic agents, see G. H. Jones and J. Young, U.S. Pat. No. 4,229,478, issued Oct. 21, 1980 and G. H. Jones et al., J. Med. Chem., 29, 1504 (1986).
Accordingly, the present invention provides a well tolerated and effective means for preventing or relieving herpes viral infections.
The association of antiviral activity with the above-noted naphthoquinone derivatives is an unusual finding. On a structural basis, it represents a departure from the chemical structures of compounds usually associated with antiviral activity, such as purine and pyrimidine nucleosides, 1-adamatanamine, particular interferons, etc. Two naphthalene derivatives, nevertheless, have previously been reported to have antiviral properties. The two naphthalene derivatives are 1,2,3,4-naphthalenetetrone, M. Y. Kraft et al., UK patent 1,243,401, Aug. 18, 1971, and 6-bromo-1,2-naphthalenedione, L. F. Stebaeva et al., Farmakol. Toksikol. (Moscow), 43, 609 (1980); Chem. Abstr., 93, 179724j (1980). The naphthoquinone derivatives of the present application are distinguished readily from the latter two naphthalene derivatives by marked structural differences arising from the substituents on their bicyclic structures.